title: Cellular therapy to target neuroinflammation in amyotrophic lateral sclerosis.
abstract: Neurodegenerative disorders are characterized by the selective vulnerability and progressive loss of discrete neuronal populations. Non-neuronal cells appear to significantly contribute to neuronal loss in diseases such as amyotrophic lateral sclerosis (ALS), Parkinson, and Alzheimer's disease. In ALS, there is deterioration of motor neurons in the cortex, brainstem, and spinal cord, which control voluntary muscle groups. This results in muscle wasting, paralysis, and death. Neuroinflammation, characterized by the appearance of reactive astrocytes and microglia as well as macrophage and T-lymphocyte infiltration, appears to be highly involved in the disease pathogenesis, highlighting the involvement of non-neuronal cells in neurodegeneration. There appears to be cross-talk between motor neurons, astrocytes, and immune cells, including microglia and T-lymphocytes, which are subsequently activated. Currently, effective therapies for ALS are lacking; however, the non-cell autonomous nature of ALS may indicate potential therapeutic targets. Here, we review the mechanisms of action of astrocytes, microglia, and T-lymphocytes in the nervous system in health and during the pathogenesis of ALS. We also evaluate the therapeutic potential of these cellular populations, after transplantation into ALS patients and animal models of the disease, in modulating the environment surrounding motor neurons from pro-inflammatory to neuroprotective. We also thoroughly discuss the recent advances made in the field and caveats that need to be overcome for clinical translation of cell therapies aimed at modulating non-cell autonomous events to preserve remaining motor neurons in patients.
authors.affiliation: Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca'Granda Ospedale Maggiore Policlinico, 20135, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Rizzo
authors.forename: Giulietta
authors.initials: G
authors.lastname: Riboldi
authors.forename: Sabrina
authors.initials: S
authors.lastname: Salani
authors.forename: Monica
authors.initials: M
authors.lastname: Nizzardo
authors.forename: Chiara
authors.initials: C
authors.lastname: Simone
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
authors.forename: Eva
authors.initials: E
authors.lastname: Hedlund
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000637:transplantation*; D019556:COS Cells; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000628:therapy; D008264:Macrophages / Q000276:immunology; D051379:Mice; D017628:Microglia / Q000378:metabolism / Q000637:transplantation*; D009046:Motor Neurons / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*